Afterreading the wholegenome of humans,researchersturned their attention to the diversity of humanorganisms at the genomiclevel.Humansproducegametes by meiosis, during which genetic recombinationoccurs.In addition,DNA is sometimesdamaged by ultravioletradiation and oxidative stress,causing a mutation in the base sequences. If such a mutationoccurs in a germ cell, it will be transmitted to subsequentgenerations. This kind of geneticmutation and recombination is repeated in the genomic sequence.Thus, the genomic sequence is unique and varies slightly from person to person.Single Nucleotide Polymorphisms (SNPs*14 ) are common in the human genome.Nearly 10 millionSNPs have been submitted to databases.Simplecalculationsshow that 1 in 300 bases has an SNP.Bothgenetic factors and environmental factors must be considered as factors in human development.Regardinggenetic factors,individual differences are expressed as phenotypes by the accumulation of mutations and polymorphisms such as SNPs.

*14 Pronounced "snip"

The Right to Know and to Not Know

Now that the human genomeproject has been completed, the responsible genes for many genetic diseases are beingdiscovered at the DNAlevel. Today, it is easy to find out whether a mutation that causes a genetic disease is present in a person's DNAjust by takingDNA from a person and analyzing its sequences.
This situationcan be considered an example of scientificprogress, but is this always a good thing? How would you feel if you analyzed your ownDNA sequences and found a disease-causing geneticmutation?
Such situationspose the problem that knowinggenetic information is not in itself an advantage.Presently, the "right to know" and the "right not to know" the results of geneticdiagnoses are bothaccepted.

ColumnFig. 3-1. GeneticMutations and FamilyLineage

In this family tree, the circles are females and the squares are males. The blacksymbolsrepresentcarriers of the disease-causing geneticmutation "A." The numeralsindicateage. The diagonallinesrepresentmembers who have alreadydied. This genetic disease is transmitted as a dominanttrait. The question is whether the mother in this family tree(indicated in red)may or may not carry the geneticmutation.

However, the "right to know" and the "right not to know"involve much more difficultproblems than expected.Consider the followingexample.
A womanvisited a doctor and told him, "My motherpassed away because of a genetic disease.Now that the human genomeproject has been completed, the responsible gene for the genetic disease has been identified. This diseasegenerallyoccurs in 1 in 100,000 people, but since it is a dominanttrait, a person who has a parent with this disease has a 50:50 chance of developing it. Now I have reached the sameage at which my motherdeveloped the disease, and I'm very worried that I mightdevelop it too.Family and friends keeptelling me that I should have genetic testing done. But if the samemutation that caused my mother's disease is discovered in my DNA, I don't think I'll have the courage or confidence to face that reality.Even from a socialperspective, I'm frightened."
In response to this request, the doctorsaid "Your right not to know has now been established. You don't have to be tested" and sent her home.However, this woman had a daughter, and she wanted to knowwhether she woulddevelop the samegenetic disease that her grandmother had. Given recentprogress in modernmedical science and technology, she knew an earlierdiscoverywouldlead to a bettertreatment.Since no one in her father's ancestralline had had this genetic disease, the daughter did not have to worry about whether she woulddevelop the disease if her mother did not have the geneticmutation that caused it. Therefore, the child wanted her mother to receivegenetic testing, but her mother did not want to be tested.
In exasperation, the daughterbrought her ownDNA to the hospital without telling her mother and receivedgenetic testing. The resultsshowed that the responsible genemutation was present in her DNA.Since this geneticmutation was thought to have come from her mother, this also meant that her mother was a carrier of the mutation.Thus,even when a personopts for the right not to know, her rightcannot be protected if otherpeople do not recognize it. We nowneed to understand that genomic information is not just a matter for the person who is at the risk of developing a genetic disease.

3.4.2

Species Differences:DifferencesbetweenChimpanzees and Humans

Next, let us comparehumans with another species—chimpanzees. We canprobablythink of many differencesbetweenchimpanzees and humans, such as the use of complextools, high-level language, and the so-calledculturallife.However, a comparison of genomes in chimpanzees and humansreveals that almost 99% of the DNA sequences of these two organisms are the same, and only 1.23% are different.On the other hand, if we compare the genomicstructure, we canseeobviousdifferencesbetweenhumans and chimpanzees. The chromosomes that make up the human genomeconsist of 22 pairs of autosomes and X and/or Y sex chromosomes, but chimpanzees have one additionalautosome,making a total of 23 pairs of autosomes and X and/or Y sex chromosomes (Fig. 3-10A). Furthermore,fragments of chimpanzeechromosome numbers 12 and 13 are linked on human chromosomenumber 2 (Fig. 3-10B). It is thought that large-scale genomic DNArecombination had occurred over the generations in ancestorscommon to humans and chimpanzees until these two chromosomesfused and became one. Humans are thought to be descendants of a new organism that divergedafter such a change in chromosomalstructure.Furthermore,comparisons of proteinsexpressed in humans and chimpanzeesshow that many of these proteinscontainamino acid substitutions,indicating that there are differences in proteinfunctionsbetweenhumans and chimpanzees.

Fig. 3-10. A Comparison of Genes in Humans and Chimpanzees

(A) Genomesize.Humans and chimpanzees have about the samenumber of genes, but a differentnumber of chromosomes.Consequently, the two speciescannotproduceoffspring.
(B) Chromosome 2 in humans is formed by a fusion of chimpanzeechromosomes 12 and 13.

Consanguineous Marriage

In humans, the father and mothereachtransmit one set of chromosomes to their child;consequently, there is a 1/2 probability that a specific gene in the childwillcome fromeitherparent during gameteformation.
With this fact in mind, let us nowmake a family tree (ColumnFig. 3-2). Grandparents give birth to somechildren.Suppose that two grandparents have children, who then eachgetmarriedseparately and have children of their own. These childrenwill be each other's cousins. If these cousinsmarryeach other, what willhappen if they have children?
As an experiment, let us calculate the probability that two copies of one specific gene on one specificchromosome in the grandmother will be transmitted to a greatgrandchild whose parents are cousins.Gametes are formed three times—when they are passed from the grandmother to the father, from the father to the grandchild, and from the grandchild to the greatgrandchild. The probability that one specific gene on one specificchromosome of the grandmother will be passedthrough her son to her greatgrandchild is 1/23 = 1/8. Similarly, the probability that the genewill be passedthrough her daughter to her greatgrandchild is 1/8. Therefore, the probability that two copies of one specific gene on one specificchromosome are passed from the grandmother to her greatgrandchild is 1/8 × 1/8 = 1/64.Since the grandmother and grandfather each have two copies of the chromosome*15, the probability that two copies of the samegene from the same grandparents will be transmitted together to a grandchild whose parents are cousins is generally 1/64 × 4, or 1/16. The numberobtained by this calculation is called "inbreeding coefficient," and an inbreedingcoefficient of 1/16 is used for marriagesbetweencousins.

ColumnFig. 3-2. Family Tree of MarriagebetweenCousins

Calculation of the probability that a specific genewill be passed on from the grandmother and grandfather to their greatgrandchild.

If the frequency of expression of a recessive gene that causes a genetic disease is 1/1,000, the probability of becoming homozygousrecessive as a result of an arbitrarymarriage is 1/1,000 × 1/1,000 = 1/1,000,000. When two cousinsmarryeach other, the probability that their child is homozygousrecessivewill be approximatelyequal to the probability 1/1,000 that one of the grandparents has the recessive gene, which is then multiplied by the inbreedingcoefficient of 1/16*16. In other words,cousins are 60 to 65 times more likely than the unrelatedcouples to produce a homozygousrecessivechild.
The probability of producing a child who is homozygous for a genesteadilyincreaseseach time a consanguineous marriagerepeats.Japaneselawcurrentlyallowsconsanguineous marriagebetweencousins, which have an inbreedingcoefficient of 1/16, but prohibitsconsanguineous marriage with a higherinbreedingcoefficient.

Repetition of Replication and Mutation:Diversity and Evolution of Life

Eversince the first primitivelifeappeared and retainedDNA as genetic information,organisms have been continuallyrepeatinggenetic recombination. This genetic recombinationforms new genes.In particular,sincesexes became established,genetic diversity has sharplyincreasedthroughgenetic recombination,overlaps, and deletions during the formation of gametes. When there is an exon–intron structurefound in eukaryotic cells, and genetic recombinationoccurs in the intron, a new gene is sometimesformed at the front and rearparts of a gene(seeChapter 4).
The genetic recombination that occurs during the formation of gametesgeneratesdiversity in the form of differencesbetweenindividualorganisms. When such diversityexceeds a threshold and an organismloses its ability to breed, a new specieswill come into existence. This is how diversity as speciesbegins (Fig. 3-11). Humans and chimpanzeesprobablydiverged from a commonancestor while repeatingreplication and mutation of the genome in this manner.

Fig. 3-11. Schematic Diagram of the Diversity and Evolution of Life

In any given species, there is diversity at the genomiclevel. If this diversityexceeds a threshold,compatiblegametescannot be passed on, and a new speciesarises.Diversity once againincreases in the new species.

At the same time, this processsuggests that even we humansmay not continue to exist forever. Replication and mutation are repeatedwheneverhumansleavedescendents. Such a processproducesdiversity in humans, but if this diversityexceeds a certainrange, it is possible that a new species of organismwilldiverge from humans.
The globalenvironmentwillprobablycontinue to changein future.Even if many species or organisms become extinct,as long as there is diversity of life,somespecieswilladapt to the changes and survive, and diversitywilllikelyincrease again.The repetition of replication and matation is the driving force of diversity and evolution of life.

The Genome and Society

Achievements of science and technology in readinggenome sequencesalreadybenefit us in our lives.
The word "genome" brings to minddiseases and medicaltreatment. Of course,genomic informationcan be used in medicaltreatment to determine the diagnosis of a genetic disease. We may also hearnews about genes for longevity, and this is also an example of how genomic information is tied to our lives.
A more familiarexample is foodtesting. It is possible to perform a DNAtest on whetherbeeflabeled as a certainbrand or as a product of a particularregion is actually what it claims to be. What can be covered up by externalappearancescannot be done so by DNA sequences.
When a crime has been committed, it is possible to identify the criminal with high certainty by testingDNA on an item that belongs to a suspect. This testingcan be performed on minute quantities of cells.Determination of parentage can also be performedaccording to the sameprinciple.
Such a testmainlyuses a laboratorytechniquecalledPCR(seeChapter 11). Because of the importance of this technique, the Nobel Prize in Chemistry was awarded to its developer,KaryBanks Mullis, in 1993.
A breed of cattlecalled Belgium Blue is highlyvalued for its muscularity and high-quality meat. The high quality of such meat is caused by a mutation in a genecalledmyostatin. Once genomic sequences are completelyknown, the use of DNA-sequence information is expected to progress.